Maternal body mass index in pregnancy and offspring asthma and food allergy
Authors: Mwenya Mubanga, Bronwyn H. Brew, Hanna Karim, Philip Curman, Anna Hedman, Cecilia Lundholm, Catarina Almqvist
Journal: Allergy (2023)

To the Editor, Asthma and food allergy (FA), like other atopic conditions, co-occur.1 Early life exposures may be common risk factors for both, triggering physiological pathways for both asthma and FA.2, 3 Maternal obesity is a known risk factor for conditions in both mother and child, impacting fetal programming and health in early childhood.4 Furthermore, maternal overweight during pregnancy may also play a role in both childhood respiratory health and allergic disease.5 However, studies report inconsistent associations between maternal BMI and asthma and FA, and potential confounding from shared familial factors remains uncertain. We investigated the association between maternal body mass index (BMI) and offspring asthma and FA in a population-based study with a sibling sub-population analysis. We identified 1,389,842 Swedish children born between 2006 and 2019 from the Swedish Medical Birth Register and followed them up until December 2021. We defined asthma using ICD-10 codes (J45-J46) or dispensed asthma-medication according to pre-defined criteria in the Prescribed Drug Register. FA was defined as physician-confirmed IgE-mediated ICD-10 codes (Z91.0A-E) or medication-defined based on adrenaline dispense (ATC-code C01CA24). Maternal BMI was constructed from antenatal booking measurements and categorized as underweight (BMI < 18.5), healthy weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30) and obese (≥ 30). In additional analyses, BMI was included as a continuous variable. Relationships were estimated using Cox proportional hazards regression with attained age as analysis timescale with time varying effects where follow-up time was divided into two intervals <3 or ≥3 years. Analyses were performed using STATA 16 (Stata Corp). Of 1,389,842 eligible children, 143,123 (10.3%) developed asthma. Maternal overweight and obesity were associated with increased risk of offspring asthma (age <3 years: adj-HR 1.15, 1.13–1.17 and adj-HR 1.35, 1.32–1.38; and for age ≥3 years adj-HR 1.09, 1.07–1.11 and adj-HR 1.24, 1.21–1.27, respectively). For FA in children aged ≥3 years, maternal overweight and obesity was associated with a lower hazard ratio In sibling control analysis, associations remained for asthma both before and after 3 years of age (adj-HR 1.15, 1.06–1.25 and adj HR 1.17, 1.06–1.30) for maternal obesity, however they did not remain for FA, Figure 1. Similarly, when maternal pregnancy BMI was modelled as a continuous exposure, for children age <3, there was an increased risk of offspring asthma and a lower risk of any FA with higher BMI, Table 1. For children aged ≥3, higher BMI was associated with increased hazard of offspring asthma and lower hazard of any offspring FA, Table 1. In the sibling analyses only the estimates for asthma remained. Model 1 HR (95% CI) Model 2 HR (95% CI) Sibling Model HR (95% CI) Similar to us, in a Danish study (n = 38,874), maternal BMI was associated with increased risk of asthma/wheezing.6 Further, an American study found that higher pre-pregnancy BMI was associated with increased offspring FA in middle childhood (adj-RR, 1.72; 1.18–2.51), but not early childhood (adj-RR, 0.84; 0.57–1.23).7 Although the association between raised maternal BMI and FA in our population appears inverse, when adjusting for shared confounders in the sibling comparison, the association changes such that there is a positive association between maternal obesity and FA in children <3 and attenuates in children >3 years. This suggests that familial confounding may affect maternal obesity-FA associations differently to maternal obesity-asthma associations. Limitations to our study include an inability to adjust for maternal FA or diet. However, strengths include a large population, the use of multiple definitions for FA and our ability to conduct a sibling analysis which controls for some familial confounding. In summary, maternal overweight and obesity in pregnancy is associated with an increased risk of offspring asthma but any association with FA is likely confounded by familial factors. Conceptualization: CA, CL, AH, MM; Methods: CL, BHB, PC, MM, HK, CA; Data Analysis: MM, CL; Funding: CA, Manuscript first draft: MM, CA, CL Manuscript Revision MM, BHB, HK, PC, AH, CL, CA. The authors thank all the members of the Catarina Almqvist research group for their advice on study design and analysis. Funding for this project was received from the Swedish Research Council (grant no 2018–02640), the Swedish Asthma and Allergy Association and the Swedish Heart and Lung Foundation. The authors report no conflict of interest. The data that support the findings of this study are available on request with ethics permission from the Principal Investigator. The data are not publicly available due to privacy or ethical restrictions. Data S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.